Iadademstat + SBRT + Atezolizumab for Small Cell Lung Cancer

(TIARA Trial)

Overseen By Carole Ramm

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Tranylcypromine, Phenelzine

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for individuals with small cell lung cancer (SCLC) that has recurred or persisted after initial chemotherapy. The researchers aim to determine the optimal dose of iadademstat, a drug under investigation, combined with atezolizumab, an immune-based therapy, to assess if this combination effectively controls the cancer. This trial suits those with SCLC that has not significantly progressed after platinum-based chemotherapy and who have at least one tumor suitable for targeting with stereotactic body radiation therapy (SBRT). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like antidepressants with specific activity and systemic immunosuppressive medications are restricted. It's best to discuss your current medications with the trial team to ensure they don't conflict with the study requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of iadademstat and atezolizumab is still under study for safety. In ongoing trials, researchers test this combination to determine the safest and most effective dose. The goal is to see if iadademstat can help control cancer for a longer time when used with atezolizumab.

Although detailed safety information is not yet available, the presence of iadademstat in a phase 1 trial indicates that scientists are still learning about its safety in humans. This phase primarily assesses how well people tolerate the treatment and what side effects might occur. Participants receive close monitoring to manage any side effects.

In summary, while scientists remain hopeful about the potential benefits, the safety of iadademstat combined with atezolizumab is still under investigation. Participants in these trials play a crucial role in determining how safe and effective this treatment might be. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Iadademstat is unique because it targets a specific protein, LSD1, which is involved in the growth and spread of small cell lung cancer (SCLC). Unlike traditional chemotherapy that broadly attacks fast-growing cells, Iadademstat's precision can potentially lead to fewer side effects and more effective tumor control. Researchers are excited about this treatment because it can be combined with Atezolizumab, an immunotherapy drug, to enhance the body's immune response against cancer cells, offering a novel approach that could improve outcomes for patients with SCLC.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

In this trial, participants will receive a combination of iadademstat and atezolizumab. Previous studies have shown that adding iadademstat to atezolizumab can stabilize cancer for longer periods compared to using atezolizumab alone. Iadademstat blocks LSD1, an enzyme necessary for cancer cell growth, which may enhance the effectiveness of immune treatments like atezolizumab. Early findings suggest that this combination could improve outcomes for patients with small cell lung cancer (SCLC). Although more research is needed, these early results are promising for treating SCLC. ^{1 3 5 6 7}

Who Is on the Research Team?

Annie Chiang, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for people with a certain type of lung cancer (ES-SCLC) that's come back or hasn't gone away after platinum-based chemo. It's also open to those who've had stable disease post initial treatment, even if they've tried immune checkpoint inhibitors before.

Inclusion Criteria

My small cell lung cancer has worsened or not improved after platinum-based treatment.

Participants must agree to submit blood samples for exploratory biomarker research at the times identified in the study calendar

Signed informed consent form

Exclusion Criteria

My high blood pressure is not under control.

I have had cancer spread to the lining of my brain and spinal cord.

My cancer spread is not causing pain or affecting my functions yet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Treatment

Participants receive iadademstat combined with atezolizumab and SBRT. Dose escalation and de-escalation will be guided by the BOIN design.

28 days per cycle, until unacceptable toxicity or loss of clinical benefit

1 visit per cycle (in-person)

Maintenance Therapy

Participants receive maintenance therapy with iadademstat and atezolizumab after initial treatment phase.

28 days per cycle, until unacceptable toxicity or loss of clinical benefit

Follow-up

Participants are monitored for safety and effectiveness after treatment. Includes survival follow-up visit 30 days post end of treatment.

30 days post end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Iadademstat
• SBRT

Trial Overview The study tests Iadademstat combined with SBRT (a targeted radiation therapy) and Atezolizumab, an immunotherapy drug. Since it's phase 1b, the focus is on finding the right dose of Iadademstat that’s safe when given with SBRT and Atezolizumab.

How Is the Trial Designed?

Group I: Iadademstat + Atezolizumab Experimental Treatment 3 Interventions

The first three participants will start iadademstat at a dose of 600ug PO weekly (DL 1). Dose escalation and de-escalation will be guided by the BOIN design. Dose finding will continue until the pre-specified sample size of 15 is reached or stop the trial if the number of participants treated at the current dose reaches 12 and the decision is to stay at the current dose. Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1680mg on Day 1 of each 28-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the treating investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status (e.g., symptomatic deterioration such as pain secondary to disease).

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Oryzon Genomics S.A.

Industry Sponsor

Trials

5

Recruited

350+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06287775?term=NCT06287775&rank=1

NCT06287775 | Testing the Combination of an Anti-cancer ... Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01398

Testing the Combination of an Anti-cancer Drug ... Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients ...

3. oryzon.com oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-phase-iii-clinical-trial

ORYZON announces first patient dosed in NCI-sponsored ... The first patient has been dosed in a Phase I/II trial of iadademstat, Oryzon's potent and selective LSD1 inhibitor, in combination with immune checkpoint ...

4. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/oryzon-doses-first-patient-in-iadademstat-trial-in-small-cell-lung-cancer/

Oryzon Doses First Patient in iadademstat Trial in Small ... Positive results could significantly alter the treatment landscape for SCLC and potentially pave the way for accelerated regulatory pathways.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07113691

NCT07113691 | Iadademstat + SBRT With Atezo in ES-SCLC The primary objective is evaluating the safety, tolerability and efficacy of iadademstat combined with atezolizumab and SBRT followed by ...

6. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/cirb242205

CLINICAL TRIAL / NCT06287775 This phase I/II trial tests the safety, side effects, and best dose of iadademstat when given together with atezolizumab or durvalumab.

7. trialx.com trialx.com/clinical-trials/listings/319698/testing-the-combination-of-an-anti-cancer-drug-iadademstat-with-other-anti-cancer-drugs-atezolizumab-or-durvalumab-at-improving-outcomes-for-small-cell-lung-cancer/

Testing the Combination of an Anti-cancer Drug ... Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in ...